11 research outputs found

    <i>P</i>. <i>mirabilis</i> treatment alters markers of hypoxia in the tumor microenvironment.

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    <p>(A) Western blotting demonstrated reduced expressions of CA IX and HIF-1a in the bacteria treatment group after 21 days of treatment; (B) The result was confirmed by immunohistochemistry for CA IX and HIF-1a in tumor sections of treated and control mice. CA IX positivity was localized in the cytoplasm and HIF-1a in the nucleus. (C and D) Quantitative analysis of immunohistochemistry staining indicated that CA IX and HIF-1a expression were lower in the bacteria treatment group than those in the control group (p < 0.05).</p

    <i>P</i>. <i>mirabilis</i> suppressed spontaneous pulmonary metastases <i>in vivo</i>.

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    <p>Bacterial treatment inhibited tumor spontaneous pulmonary metastases by observing fresh lung tissues (A) at the end of the experiment. (B) Quantitative statistics of metastatic foci showed significant differences between <i>P</i>. <i>mirabilis</i> treatment group and PBS control group (n = 6) (p < 0.05). (C) Quantitative statistics showed lung weight of mice in the control group was significantly higher than those in the <i>P</i>. <i>mirabilis</i> treatment group (p < 0.05). (D) Those results were further confirmed by analyzing H&E stained sections. Data were expressed as the mean ± SD.</p

    The adherence and growth inhibition by <i>P</i>. <i>mirabilis in vitro</i>.

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    <p>(A) <i>P</i>. <i>mirabilis</i> adhered to 4T1, MDA-MB-231, MCF7, and CHO cells <i>in vitro</i>. (B) The cells were counted by stained with Trypan Blue. Bacteria treatment showed dose- and time-dependent antiproliferative effects in 4T1 cell lines (C) In the colony formation assay, <i>P</i>. <i>mirabilis</i> inhibited colony formation of breast tumor cells and CHO cells by crystal violet staining. Data were expressed as the mean ± SD.</p

    <i>Proteus mirabilis</i> inhibits cancer growth and pulmonary metastasis in a mouse breast cancer model

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    <div><p>A variety of bacteria have been used as agents and vectors for antineoplastic therapy. A series of mechanisms, including native bacterial toxicity, sensitization of the immune system and competition for nutrients, may contribute to antitumor effects. However, the antitumor effects of <i>Proteus</i> species have been minimally studied, and it is not clear if bacteria can alter tumor hypoxia as a component of their antineoplastic effect. In the present study, <i>Proteus mirabilis</i> bacteria were evaluated for the ability to proliferate and accumulate in murine tumors after intravenous injection. To further investigate the efficacy and safety of bacterial injection, mice bearing 4T1 tumors were treated with an intravenous dose of 5×10<sup>7</sup> CFU <i>Proteus mirabilis</i> bacteria via the tail vein weekly for three treatments. Histopathology, immunohistochemistry (IHC) and western analysis were then performed on excised tumors. The results suggested <i>Proteus mirabilis</i> localized preferentially to tumor tissues and remarkably suppressed the growth of primary breast cancer and pulmonary metastasis in murine 4T1 models. Results showed that the expression of NKp46 and CD11c was significantly increased after bacteria treatment. Furthermore, tumor expression of carbonic anhydrase IX (CA IX) and hypoxia inducible factor-1a (HIF-1a), surrogates for hypoxia, was significantly lower in the treated group than the control group mice as assessed by IHC and western analysis. These findings demonstrated that <i>Proteus mirabilis</i> may a promising bacterial strain for used against primary tumor growth and pulmonary metastasis, and the immune system and reduction of tumor hypoxia may contribute to the antineoplastic and antimetastatic effects observed.</p></div

    The therapeutic effect of <i>P</i>. <i>mirabilis</i> in 4T1 solid tumor model.

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    <p>(A) Bacterial treatment suppressed tumor growth at the end of the experiment. Quantitative analysis demonstrated that the volume (B) and weight (C) of tumors in the <i>P</i>. <i>mirabilis</i> and CTX treatment groups were significantly less than those in the control group (p < 0.05). Corresponding to the images in (D) and (E) quantitative analysis of Ki-67 staining further confirmed that tumor proliferation was significantly inhibited in the treatment group (p < 0.05). (F) The body weights of mice significantly decreased at the beginning of treatment, but at the end of the experiment, they were not significantly different among these groups. (J) Morphological analysis of mice kidney tissues: there were no obvious differences in morphology between the <i>P</i>. <i>mirabilis</i> treatment group and the PBS control group. Data were expressed as mean ± SD.</p
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